The ability of an animal to alter behavior in response to changes in their environment is known as flexible goal-directed behavior. Patients with neuropsychiatric disorders (e.g., addiction, ADHD, and autism) often have difficulty with this type of behavior. In the laboratory one type of task used to measure flexible goal directed behavior is a conditioned reinforcer devaluation task. In this task, animals form associations between stimuli (e.g. objects) and specific reinforcer(s) (e.g. various food rewards). The reinforcer is subsequently "devalued" by selective satiation (feeding one of the foods ad libitum). Following devaluation, normal subjects adjust their responding which reflects the new "value" of the reinforcer. The orbitofrontal cortex (OFC) in conjunction with several other brain structures (e.g., amygdala, striatum) is an important neural substrate involved in the conditioned reinforcer devaluation task. However, it is unknown if OFC is necessary for linking the decreased value of the food to the stimuli that predicts it, or guiding choices during testing. The goal of this proposal is to elucidate the neural circuitry involved in different stages of reinforcer devaluation. Specifically, the proposed experiments plan to determine the role of the OFC in reinforcer devaluation and compare and contrast the roles in rodents and non human primates. I propose to use reversible pharmacological manipulations in macaque monkeys to study the role of OFC during different stages of reinforcer devaluation (forming associations, registering a change in reinforcer value, updating reinforcer value to the stimuli, guiding choices to reflect the change in value). Reversible pharmacological manipulations provide an opportunity to delineate the role of OFC involved in individual phases of the task. In addition I plan to compare the role of the OFC in conditioned reinforcer devaluation across species. To achieve this, I developed a new rodent (rat) reinforcer- devaluation task that further reconciles the differences between the monkey and the rat tasks used to date. I also propose to study the effects of lesion in rats in the new rat reinforcer devaluation task to compare directly with previous work using various forms of reinforcer devaluation tasks in rats. Further understanding of the neural circuitry underlying flexible goal- directed behavior will help elucidate mechanisms for impairments in patients with neuropsychiatric disorders. This will provide new and more selective target systems for therapeutic intervention for individuals with maladaptive reward processing. The following aims will be used to reach my goals: specific aim 1-Determine the role of OFC in different phases of reinforcer devaluation in macaque monkeys. Specific aim 2- Determine the role of OFC in reinforcer devaluation in rats. A direct comparison OFC across species in a specific reinforcer devaluation task will enhance our understanding of the neural circuitry involved in flexible goal directed behavior. PUBLIC HEALTH RELEVANCE: Patients with addiction, autism, or attention deficit hyperactivity disorder are impaired in adjusting responding based on consequences. These types of deficits are studied by measuring the ability of a subject to alter behavior based on changing outcomes. The goal of this proposal is to further understand the role of a specific brain structure (orbitofrontal cortex) using a task which measures changing behavior.